Oral administration of pharmaceuticals and nutritionals is one of the most popular methods of delivery of such beneficial agents. Liquid suspension dosage forms are a preferred route of such oral administration for both children and adults who have difficulty swallowing capsules or tablets. Furthermore, infants cannot be given tablets or capsules. Palatability of the ingested material is an extremely important factor in ensuring the likelihood that the recipient will ingest the pharmaceutical or nutritional. Accordingly, masking of the unpleasant taste characteristics of the pharmaceutical or nutritional is an important factor in the formulation of these agents. Further, the stability of the liquid suspension is an extremely important factor. As used herein and in the claims the term "stability" means the ability of the liquid suspension to mask the unpleasant taste of the encapsulated material for a significant period of time prior to ingestion. In other words, use of the claimed composition results in minimal leakage of the active substance into the suspending medium. Additionally, after ingesting the pharmaceutical or nutritional supplement, it is often times desirable for the nutritional or pharmaceutical to be immediately available to the person in need of same.
Because of the strong, unpleasant taste of many pharmaceuticals or nutritional supplements, flavorings, either alone or in combination with sweeteners and other additives, have been employed to improve taste and palatability. The formulation of a pleasant-tasting and palatable product through the sole use of flavorings, sweeteners and additives, however, has been unsuccessful when using beneficial agents which have a particular bitter taste, such as the macrolide family of antibiotics, in particular erythromycin and clarithromycin. Attempts have been made to formulate these antibiotics into suspension dosage forms or into taste-masked chewable tablets using known coating or encapsulation processes with very limited success.
Japanese Kokoku Shu 45-12759, published Nov. 1, 1967, teaches that a mixture of 90-99% zein and 1-20% hydroxypropylmethylcellulose (HPMC) may be used to coat tablets for taste and odor masking. The application employs the high molecular weight polymeric HPMC component (exemplified at levels of 10% and above) for its film-forming properties, in a coating used to prevent the disintegration of Vitamin C as measured by temperature and time. This reference teaches that HPMC must be mixed with zein to obtain taste masking properties.
U.S. Pat. No. 3,939,259, issued Feb. 17, 1976, employed prolamine from corn grain protein (i.e. zein), with approximately an equal level of shellac and a lesser amount of ethylcellulose, to coat digitoxin particles, but did so in an attempt to achieve a sustained release effect. Since the incorporation of ethylcellulose may interfere with absorption of the active agent in a timely manner, its incorporation into the composition of the present invention for an immediately available agent would be unsuitable.
U.S. Pat. No. 4,384,004, issued on May 17, 1983, discloses the encapsulation of the artificial sweetener, L-aspartyl-L-phenylalanine methyl ester, with additional coating materials, which may include zein, for increasing shelf life stability.
U.S. Pat. No. 5,098,718, issued on Mar. 24, 1992, discloses a coating composition, consisting of very broad ranges of zein, a hydrophobic substance, an inorganic filler and an optional filler and an optional non-water soluble polymer, for coating feed additives which are intended for ruminants. The coating composition claimed in this patent is stable in the rumen and not substantially degraded in the abomasum of a ruminant, but is primarily degraded by the enzymes present in the small intestines of a ruminant. This delayed release would also be a problem when immediate bioavailability is desired.
U.S. Pat. No. 5,160,742, issued on Nov. 3, 1992, discloses a dual coating composition for sustained delivery of an active substance, said composition comprising at least a coating of prolamine and an enteric compound.
In comparison with these known formulations, the present invention provides a simple, inexpensive taste-masked stable product in suspension, while providing immediate bioavailability. This taste masking ability, without delaying release of the beneficial agent, is realized with a single coating layer of a simple, inexpensive formulation consisting predominantly of a prolamine fraction of grain, with low to moderate molecular weight plasticizer needed to form the film coating.